PROJECT SUMMARY Intestinal fistulas are a major cause of morbidity and have significant impact on quality of life. Perianal fistula development among pediatric Crohn?s disease patients is poorly understood, but develops in more than 1 in 3 children with Crohn?s disease. The relative effectiveness of different medication strategies for preventing perianal fistulas in Crohn?s disease patients is completely unknown; there are no tested strategies to preclude these devastating complications. One major limitation to studying fistulas is that the diagnosis and procedure codes pertaining to perianal fistulas are non-specific and often are not used. We recently developed and validated a new administrative claims-based case definition to more accurately identify perianal fistulas. Our long-term goal is to develop strategies to prevent perianal fistulas in patients with Crohn?s disease. The overall objective of this application is to apply our validated case definition for perianal fistulas to identify medical treatments associated with a decrease in fistula development. Our central hypothesis is that specific medication patterns will be associated with reduction in perianal fistula development among pediatric patients with Crohn?s disease. The rationale for this proposed research is that we be enabled to design prospective studies aimed at fistula prevention once we identify the medications associated with reduced fistula development. We plan to test our hypothesis and accomplish our objective by pursuing the following two specific aims: 1) To determine the relative contribution of factors associated with perianal fistula development among pediatric patients with Crohn?s disease in a national administrative claims database; and 2) To determine medications associated with prevention or delay in perianal fistula development. Building on our previous work, we will accomplish the first aim by applying our validated alternative case definition to accurately identify patients with perianal fistulas from claims data. Under the second aim, we will determine which specific medication patterns are associated with reduction or delay in perianal fistula development among pediatric patients with Crohn?s disease. We will use propensity score-based analyses to minimize the inherent bias associated with treatment allocation. The expected contribution of the proposed research is to develop evidence for identifying subgroups of pediatric patients at increased risk of perianal fistula development and the extent to which different medications are associated with differential rates of perianal fistula development. This contribution will be significant because, if successful, it is an important step toward much-needed evidence for individualizing medical therapy for prevention of fistulas in pediatric Crohn?s disease. The proposed research is innovative, because it evaluates population-based comparative effectiveness strategies to prevent perianal fistulas among a large cohort of pediatric Crohn?s disease patients. This has never been accomplished previously due to inadequate samples and the limited accuracy of previously applied case definitions.